JP2009507016A - Novel skin care composition - Google Patents

Abstract

Skin care comprising a highly hydrophobic material, an alkaryl polyfluorocarbon, especially a substituted phenyl-polyfluoroacylaminopropanamide, an alkanol, and an amount of refined oil and triglyceride fraction of oil sufficient to provide substantial homogeneity A composition is provided. When used for hirsutism, an antioxidant and a humectant are optionally added. For use against wrinkles, there are mixtures of additional vitamins, antioxidants, and natural substance extracts.

Description

  This application claims priority from US Provisional Patent Application No. 60 / 713,882, filed Sep. 1, 2005, which is incorporated herein by reference in its entirety.

  The present invention was not made with government support.

  There are no references to sequence listings, computer programs, or compact discs.

  The field of the invention relates to cosmetic compositions, in particular skin care involved in hormonal upset of the skin.

  Related properties such as growth and loss of mammalian skin and wrinkles and hair are significantly affected by individual skin responsiveness to hormones and levels and ratios of hormones and are of great interest in the treatment of skin and related properties There are numerous reports of treatment as palliatives and therapeutics.

1. Wrinkle removal wrinkles are skin caused by thinning of the skin and loss of elasticity as a result of physical factors such as aging and / or exposure to harmful substances and / or UV rays that adversely affect skin metabolism Folds and wrinkles. Wrinkles are not a medical condition and formulations are classified in the cosmetics field as long as the substances used to treat the wrinkles are not systemically reabsorbed and are not systemically active.

  Although there are many requirements for the invention for non-surgical wrinkle removal or removal, there are few systematic studies that address such requirements. Large amounts of facial creams containing various substances are commercially available, many of which are ineffective or induce side effects at the level of effectiveness. Thus, topical vitamin C, tretinoin or isotretinoin temporarily improves wrinkles caused by aging and photodamage, but is known to have a significant incidence of irritation. Induction of dysparalysis of muscle fibers for cosmetic purposes by substances that block the neuromuscular junction is physiologically unacceptable and has specific toxicity.

  Local and / or systemic use of human-derived estrogen increases skin mucopolysaccharide concentration that increases skin collagen content and increases skin thickness, as well as directly reduces wrinkle depth Presented as letting However, systemic administration of mammalian estrogens for the sole purpose of reducing the signs of skin aging is not medically protective. Dermatologists have studied topical estriol and 17-β-estradiol and have not only found reduced wrinkle depth and increased hydration, but systemic absorption, regardless of extent, can also lead to the production of prolactin. (Schmidt et al., 1996, Int J Dermatol, Vol. 35, No. 9, p. 669-74). Thus, topical mammalian estrogens for skin regeneration are effective but cannot qualify as cosmetics and are not approved in cosmetic creams. Certain phytoestrogens found in various plants as flavonoids, especially isoflavones, have been shown to have even lower effects than mammalian estrogens. However, in topical use they are not resorbed systemically (Bayerl and Keil, 2002, Akt Dermatol, 28, p. 14-8).

  There are many combinations of different ingredients in cosmetics such as antioxidants, enzymes, phytoestrogens, emollients, moisturizers and the like. The ability to protect the skin and reduce wrinkle formation varies with the composition and its components.

  Therefore, it reduces the occurrence of wrinkles, has minimal or no side effects such as erythema, edema or irritation, is not systemically reabsorbed when applied to the skin, and does not change the color of the skin, for example There is a need for safe and effective cosmetics that are substantially transparent when applied.

2. Compositions that affect female facial hair growth (sequel hirsutism) Approximately 8% of females have idiopathic hirsutism (IH), an excessive male-like pattern without potential systemic endocrine pathology Suffers from hair growth. IH is characterized by a higher sensitivity of hair follicle androgen receptors to androgens, or higher skin androgen concentrations. IH is regarded as a hyper-androgen syndrome in the cosmetics field, especially because black excessive facial hair is visible and causes psychological distress.

  State of the art treatments are local and / or systemic drug therapies in combination with mechanical removal including shaving, hair loss, dead hair treatment, plaking, laser, ultrashort pulsed light and / or electrolysis treatment. Only when IH occurs simultaneously is metformin known to be often associated with gastrointestinal side effects, mainly antidiabetic drug treatment.

  Androgen targeted drugs improve female IH by inhibiting male hormone synthesis, such as inhibition of testosterone conversion to dihydrotestosterone (by finasteride) or blocking androgen receptor. Finasteride and antiandrogens are contraindicated in women of childbearing age as they cause feminization of male fetuses. Cyproterone acetate (CPA), a luteinizing hormone drug with antiandrogenic properties, poses a risk of hypertension, thromboembolism, diabetes, hypercholesterolemia and endometrial cancer. Steroid-structured antiandrogens for topical use have recently been published (see Labrie et al.). Non-steroidal blockers of the androgen receptor, such as flutamide or bicalutamide, block androgen binding. When tested locally in male androgenetic alopecia, nonsteroidal blockers have proven to be substantially systemically resorbed and these have not been approved for IH treatment. Despite the local testing of the antiandrogens RU588841 and RU56187, ie N-substituted arylhydantoins or thiohydantoins, they were converted systemically into common metabolites of strong antiandrogens. Topical eflornithine suppresses the conversion of ornithine decarboxylase, and thus ornithine to putrescine, and regulates the growth phase of hair development.

  Mechanical hair removal by pulling with tweezers and hair removal drugs stimulates the growth of thick and coarse hair, makes subsequent treatment more difficult, and sometimes induces folliculitis and trauma to the hair shaft and skin, IH can potentially be exacerbated.

  Although IH can be considered a medical condition, the formulation is in the cosmetics field as long as the substance used to treat IH is not reabsorbed into the body so that it is systemically active. A topical cosmetic composition that is not absorbed systemically, reduces hair diameter, color, and growth rate and does not change the appearance of the skin would be advantageous for women suffering from unwanted hair.

  With regard to wrinkles, the use of natural extracts and their fractions has found widespread use in cosmetics: resveratrol, WO 04 / 026,222, 01/30314, Glycine Soya, USA Patent Application Nos. 2004/0191350, 2005/0048105, 2005/0112153, Grape Seed Oil, WO 01/17495, Bosveria Serata, US Patent Application No. 2005/01213559 and International Publication No. 00. / 0578393 pamphlet and Cocos Nusifera, US Pat. No. 6,551,656. Fleuridil has already been used in formulations useful for various conditions where effects on skin receptors are desirable (US Pat. No. 6,184,249, specifically incorporated herein by reference, Sovak et al. WO 01/58854; 2002, Dermatol Surg, 28, p. 678-85; Seligson et al., 2003, Drug Dev Res, 59, p.292-306).

  Interesting references regarding wrinkle treatment include US Pat. Nos. 5,889,054, 6,139,829, and 1,180,133. The discussion of hormone replacement is described in Sator et al., 2004, Exp Dermatol Vol. 13, Appendix 4, p. Found at 36-40.

  Regarding IH, Good Heart H. (Goodheart H.), “Hirsutism: Pathogenesis and Causes”, Women ’s health Prim Care, 2000, Vol. 3, p. 329-37; (Azziz R.), "The evaluation and management of hirsutism," Obstet Gynecol, 2003, 101, p. 995-1007; Shenenberger D, Wutekt L. (Utecht L.), “Removal of unwanted facial hair,” Am Fαm Physician, 2002, 66, p. 1907-11; and Dowbar R.A. P. (Dawber R. P.), "Guidance for the management of hirsutism," Modern Medical Research and Opinion, 2005, Vol. 21, p. See 1271-2234 (8). In addition, D.C. D. Cousty-Berlin et al., “Preliminary Pharmacokinetics and Metabolism of Novel Nonsteroidal Antiandrogens in Rats: Relationship of Their Systemic Activity to the Formation of Common Metabolites (Preliminary Pharmacokinetics and Metabolism of Novel Non-steroidal Antiandrogens in the Rat: Relation of their Systemic Activity to the Formation of a Common Metabolite,), Steroid Biochem Molec Biol, 1994, Vol. 51, p. 47-55, and Labrie et al., “Topical antiandrogenic steroids,” US 2004/0224935, 2004, 11 November.

  Cosmetics for application to the skin for the treatment of hormone-related properties are physiologically acceptable as excipients with substituted highly hydrophobic substances including alkaryl polyfluorocarbons, especially substituted phenyl, perfluoroacylamino-propanamide. Along with possible lower alkanols, it is used in conjunction with soluble additives related to treating the above specific properties, particularly refined vegetable oils and their derived triglyceride fractions. Facial care cosmetics and their use to reduce or eliminate facial hair in hirsutism women selectively use humectants. Wrinkle-removing facial care cosmetics and their use, in addition to the above, use natural extracts or fractions thereof and optionally a mixture of conventional additives, in particular antioxidants.

  The formulation is a substantially clear, non-irritating liquid that is applied topically and rapidly reabsorbed into the skin resulting in reduced wrinkles and / or hirsutism.

Facial care cosmetics are provided. These compositions contain effective amounts of alkaryl polyfluorocarbons, particularly substituted phenyls, highly hydrophobic materials consisting of perfluoroacylaminopropanamide, other ingredients that provide ancillary benefits and solubility, lower alkanols and at least one of Contains refined oil, its fractions and optionally an antioxidant (effective amount means an amount sufficient to produce a therapeutic effect). The excipient comprises a large amount of at least one refined vegetable oil and oil triglyceride fraction and a small amount of a physiologically acceptable alkanol consisting of 2 to 3 carbon atoms. Refined oils and their triglyceride fractions are present in large amounts in facial cosmetics, generally at least about 50% by weight, more typically at least about 60% by weight, and up to about 95% by weight. The refined oil may be a vegetable oil such as grape seed, rapeseed, soybean oil, and at least a fraction of the oil of Cocos Nusifera (C _6-10 triglycerides) and / or glycine soya (soy oil, medium chain triglycerides). One may be sufficient. For wrinkle removal, the composition comprises at least one plant natural extract or fraction thereof, usually a combination thereof, or a synthetic composition equivalent, at least one antioxidant, but two or more antioxidants. Contains mixtures, such as vitamins, and other additives as required. In order to reduce facial hair, the antioxidant is usually tocopherol and optionally contains a humectant.

  The formulation is at least substantially homogeneous. They are easily applied to the skin as a substantially clear liquid that does not cause irritation. The composition can be used repeatedly and safely. These formulations are not resorbed systemically. The alkaryl polyfluorocarbon compound used is preferably substituted phenyl or perfluoroacylaminopropanamide. Most of the phenyl substituents are 4-nitro-3-trifluoromethyl. A compound of particular interest is 4-nitro-3-trifluoromethylphenyl substituted perfluoroacylaminopropanamide, where the perfluoroacyl group is 2-3 carbon atoms and the propanamide group is in the 2-position At least one of hydroxyl and methyl.

［式中のＸは、ニトロ基（ＮＯ_２）、シアノ基（ＣＮ）、またはハロゲン元素、好ましくはＦ、ＣｌおよびＢｒ、より好ましくはフッ素および塩素、最も好ましくはフッ素であり；Ｖは、一般式ＣＸ_３（式中、Ｘはハロゲン元素、好ましくはＦ、ＣｌおよびＢｒ、より好ましくはフッ素および塩素である）であり、そしてＶは、最も好ましくはＣＦ_３であり；Ｚは、一般式（ＣＦ_２）_ｎＣＦ_３（式中、ｎは、０〜９、好ましくは０〜５、最も好ましくは０〜２である）である。］のものを含む。これらの化合物は、特にアンドロゲン受容体と結合し、またホルモン受容体、好ましくは皮膚中のホルモン受容体（例えば、アンドロゲン受容体）を遮断する活性を有し、細胞表面上のアンドロゲン受容体を減少し、そして局所的に塗布した際に低い全身再吸収であるが、局所的に活性である。 Compounds of particular interest are also described in the above referenced US Pat. Nos. 6,184,249 and 6,472,415. In particular, these compounds include substituted phenylalanines with 2-hydroxyl, 2-methylpropionyl and polyfluoroamide groups. These compounds have the general formula:

[Wherein X is a nitro group (NO ₂ ), a cyano group (CN), or a halogen element, preferably F, Cl and Br, more preferably fluorine and chlorine, most preferably fluorine; Formula CX ₃ , wherein X is a halogen element, preferably F, Cl and Br, more preferably fluorine and chlorine, and V is most preferably CF ₃ ; Z is the general formula ( CF ₂ ) _n CF ₃ (wherein n is 0-9, preferably 0-5, most preferably 0-2). ] Is included. These compounds specifically bind to androgen receptors and also have the activity of blocking hormone receptors, preferably hormone receptors in the skin (eg androgen receptors), reducing androgen receptors on the cell surface And low systemic reabsorption when applied topically but locally active.

  Such compounds may or may not have one or more stereoisomeric centers. The compound can be used as a mixture of racemates, or separated into its optical isomers and used as optical isomers.

  The target compound can be produced by a conventional method in which a specific treatment is changed based on a specific side group. Suitable synthetic methods are described in Seligson et al., Drug Development Research, Vol. 59, p. 292-306.

  The subject composition for wrinkle removal uses an effective amount of various physiologically acceptable natural extracts or fractions thereof, wherein the composition has a beneficial effect on the skin and / or substantially Providing a uniform composition. Extracts used include non-saponifiable fractions of vegetable oils such as Nippon Tade, Frankincense, Brassica olifera (cubes, rapeseed) and glycine soya fractions as a feed of phytoestrogens. In addition, synthetic or natural free radical scavengers, especially antioxidant vitamins, vitamins A and E, are used.

  Moisturizers for hirsutism include high molecular weight fatty acid esters with at least about 18 carbon atoms and up to 40 carbon atoms. Various types of moisturizers classified into various types can be used. Occlusive ingredients include petrolatum, mineral oil, paraffin, squalene, vegetable fat (cocoa butter), animal fat (lanolin), lanolin acid, stearic acid, lanolin alcohol, cetyl alcohol, phospholipid, silicone, etc. including. The humectant includes glycerin, propylene glycol, urea, sodium lactate, sorbitol, pyrrolidone carboxylic acid and the like. The emollients are octyldodecanol, hexyldecanol, oleyl alcohol, oleyl oleate, octyl stearate, PEG-7, glycerol cocoate, myristyl myristate, isopropyl myristate, stearyl isononanoate, isopropyl palmitate, or Contains isopropyl stearate.

  In addition, physiologically acceptable preservatives and fungicides are used in the composition primarily for storage purposes, such as sensitive components such as BHT, BHA (3-tert-butyl-4-hydroxyanisole and 2-tert-butyl-4 -A mixture of isomers of hydroxyanisole), TBHQ (tert-butylhydroquinone), ethoxyquin (6-ethoxy-1,2-dihydro-2,2,4-trimethylquinoline), propyl gallate (gallic acid, propyl ester) , Oxidation of tocopherol, rosemary extract and the like can be suppressed.

  To vary the degree, other materials having substantially the same properties for the purpose of these compositions can be substituted for the particular composition used. These ingredients are used in an amount effective to provide skin improvement, particularly a reduction in all hair except wrinkles or hair.

  Table 1 below shows the categories and ranges of materials in the skin care composition.

  Table 2 below shows the categories and ranges of materials in the hirsutism reducing composition.

  The subject compositions can be prepared using a variety of procedures and order of addition. For the wrinkle removal composition, the first mixture (A) is conveniently prepared in a polar solvent heated to a range of about 50-80 ° C, preferably 60 ° C, to which natural extract components such as resveratrol are added. Subsequently, the olibanum extract is continuously added and stirred until dissolved. The mixture is stirred until completely homogeneous and stored. Phenyl-perfluoroacylaminopropanamide is added to a triglyceride fraction (purified) of cocos nusifera oil stirred at a moderately rising temperature, usually in the range of about 35-50 ° C., and the mixture is homogenized Stir for sufficient time, usually 20 minutes. Next, vegetable oil and antiseptic antifungal agent, followed by vitamins are added to the mixture. After stirring the mixture until it can be regarded as homogeneous, the mixture (A) prepared in advance is added dropwise with stirring to prepare a concentrate that can be stored in a light-shielding container at room temperature or lower.

  For hirsutism compositions, phenyl-perfluoroacylaminopropanamide is added to a polar solvent and the mixture is stirred for a time sufficient to be homogeneous, usually about 20 minutes. Next, to this mixture is added a vegetable oil and its triglyceride fraction, optionally an antiseptic and antifungal agent, optionally followed by an antioxidant such as tocopherol. If a humectant is desired, it is added slowly with stirring, for example, dropwise, to prepare a final mixture that can be stored in a light-proof container at room temperature or below.

  Various precursor compositions having less than all components can be prepared and then the remaining components can be added.

  With the exception of other formulations, the subject formulations are usually at least substantially free of hydroxy acids, and in the case of wrinkle compositions, monocarboxylic acid esters found for use in other cosmetic compositions Is not included.

  Extracts or fractions thereof, or known active ingredients can be used. For economic reasons, it is usually preferred to use natural extracts as a source of active ingredients rather than natural sources or substantially pure products obtained from synthesis. If the active ingredient is known, the use form of the extract has at least about 50% by weight of the active ingredient and may be greater than 70% by weight. Equivalent compositions obtained from different sources have at least about 50%, usually at least about 70% of the natural extract or fractions of the solid or mixture of the main component thereof.

  Phenyl-polyfluoroacylaminopropanamide is described in US Pat. No. 6,184,249. The active compounds that can be used are substances that act on the androgen receptor in the skin but are not appreciably systemically resorbed. Such compounds are represented by 2-hydroxy-2-methyl-N- [4-nitro-3- (trifluoromethyl) phenyl] -3- (2,2,2-trifluoroacetylamino) propanamide (fluridyl). Illustrated.

  In the case of Japanese Tade extract, the extract is usually at least about 90% trans-resveratrol (CAS number: [501-36-0], 3,4 ′, 5-trihydroxy-trans-stilbene, glycone (picaide). As a)). Any other resveratrol source that provides at least a substantially equivalent amount of resveratrol can be used. Syntheticly prepared resveratrol is also acceptable.

  Frankincense, Bosveria serrata extract is a terpenoid mixture with about 60-70% triterpenes, most of which are boswellic acids, at least 10-30% (w / w) of β-boswellic acid, 5-20% (w / w) acetyl-β-boswellic acid, 5-20% (w / w) 11-keto-β-boswellic acid, and 5-20% (w / w) acetyl-11 -Keto-β-boswellic acid (CAS number [8050-07-5]). These extracts have found widespread use in food supplements and cosmetics reported in a wide variety of indications literature along with numerous successful case reports.

  Phytoestrogens are already commercially available as fractions produced from vegetable oils, rapeseed (Brassica) and / or soya (Glycine soya). In the subject formulations, a suitable vegetable oil unsaponifiable fraction (CAS number [91770-67-1]) is used as a source of phytoestrogens and is substantially free of esters.

  Grape seed oil (Vitis vinifera) or soybean oil is mainly a mixture of saturated and unsaturated fatty acids with linoleic acid and oleic acid (> 80%) as main components. These acids can be used independently of other components or synthetically prepared mixtures. These are used in the purified state.

Coconut oil (cocos nucifera) mainly provides medium chain triglycerides, where the acids are mainly C _6-10 saturated fatty acids, especially caprylic acid and capric acid (CAS number [73398-61-5]). . This is used in the purified state.

  Various antioxidants conventionally found in cosmetic formulations can be used. Commercially available forms of vitamins A and E are preferred because they are known to have beneficial physiological effects on the skin, but other antioxidants such as compounds with phenolic hydroxy functionality, ascorbic acid and its Derivatives / esters; beta carotene; catechin; curcumin; ferulic acid derivatives (eg ethyl ferrate or sodium ferulate); gallic acid derivatives (eg propyl gallate), lycopene; reducing acid; rosmarinic acid; tannic acid; Uric acid; or mixtures thereof can also be used. Other suitable antioxidants are those having one or more thiol (-SH) functional groups in reduced or non-reduced forms, such as glutathione, lipoic acid, thioglycolic acid and other sulfhydryl compounds. The antioxidant may be a mineral such as bisulfite, metabisulfite, sulfite, or other inorganic salts and sulfur-containing acids. These antioxidants can be used as partial or complete substitutes for vitamins and antiseptic preservatives, and with respect to vitamins, they are usually partial, if at all, generally applied to vitamins. Is present in less than 50%, typically less than 30% as applied to vitamins, generally up to about 2 parts, more usually at most about 1 part, while for antiseptic and antifungal agents that have antioxidant activity They can be used as a complete replacement.

  Alkanols of 2 to 3 carbon atoms, such as ethanol, propylene glycol and isopropanol, are used, in particular in amounts that provide at least substantial homogeneity to the formulation.

  Also, a small amount of antiseptic / antifungal agent is usually included, and usually no more than about three different antiseptic / antifungal agents. The antioxidant described above may act as an antiseptic / antifungal agent. More conventionally, BHT, BHA, TBHQ, ethoxyquin, propyl gallate and rosemary extracts are used.

  A particularly important aspect of the present invention is the preferred formulation as described in the Examples section. The ingredient combination is formulated so that all substances can be dissolved in a cosmetically acceptable medium. Some components, especially the extract of Bosveria serrata as well as the extract of Nippon Tade are extremely insoluble in conventional systems. The above combination forms a homogenous solution with the addition of a fraction of purified grape seed oil and the minimum amount (less than 10%) disinfecting alcohol (isopropanol) in the target mixture of medium chain triglycerides (capryl / capric acid triglyceride) To do.

  The resulting mixture is a viscous liquid with an oily appearance, yet it becomes invisible on the skin in a short time after topical application, the skin surface is not greasy, and the overall effect is high on skin softness and It is smooth.

  In addition to the ingredients listed above, there are other additives included for specific purposes. These additives and adjuvants are those commonly used in the field of beauty, pharmacy, or dermatology. For example, hydrophilic or fat-soluble gelling agents, hydrophilic or fat-soluble active agents, solvents, perfumes, fillers, fungicides, odor Absorbers, and dyes or colorants. The amounts of these various additives and adjuvants are conventional in the art and range, for example, from 0.01% to 10% of the total weight of the composition.

  Emulsifiers that can be used include glyceryl stearate, polysorbate 60, PEG-6 / PEG-32 / glycol stearate mixtures, and the like.

  Hydrophilic gelling agents include carboxyvinyl polymers (carbomers), acrylic copolymers such as acrylate / alkyl acrylate copolymers, polyacrylamides, polysaccharides such as hydroxypropylcellulose, natural rubber and clay, and also fat soluble gelling agents. Typical examples are modified clays such as bentonite, fatty acid metal salts such as aluminum stearate and hydrophobic silica, or ethylcellulose and polyethylene.

  Suitable fatty alcohols and acids include those compounds having 10 to 20 carbon atoms. Particularly preferred are compounds such as cetyl, myristyl, palmitic and stearyl acids and alcohols. Of the polyols, those that can act as emollients are linear and branched alkyl polyhydroxyl compounds. For example, propylene glycol, sorbitol, and glycerin are preferred. Also useful are polymeric polyols such as polypropylene glycol and polyethylene glycol. Butylene and propylene glycol are also useful.

  Examples of hydrocarbons that can act as emollients are those that have a hydrocarbon chain of 12 to 30 carbon atoms somewhere. Specific examples include mineral oil, petroleum jelly, squalene and isoparaffin.

  Another type of functional ingredient in the cosmetic composition of the present invention is a thickener. The thickener is usually present in an amount of 0.1 to 20%, preferably about 0.5% to 10% by weight of the composition. An example of a thickener is a cross-linked polyacrylate material marketed under the trademark Carbopol. Gum such as xanthan, carrageenan, gelatin, karaya, pectin and locust bean gum can be used. Under certain circumstances, the thickening action can be achieved with a material that acts as a silicone or emollient. For example, silicone rubber in excess of 10 centistokes and esters such as glycerol stearate are bifunctional.

  Powders can be incorporated into the cosmetic composition of the present invention. Such powders include chalk, talc, kaolin, starch, smectite clay, chemically modified aluminum / magnesium silicate, organically modified montmorillonite clay, hydrated aluminum silicate, fumed silica, aluminum starch octoctenyl. Acid esters, and mixtures thereof.

  Other minor additive ingredients can also be incorporated into the cosmetic composition. Such ingredients can be colorants, opacifiers and perfumes. The amount of such other minor additive components can range from 0.001% to 20% by weight of the composition.

  The subject composition is stored in a sealed container so as to be protected from light by making it opaque to incident light and to minimize oxygen present in the gap. In view of the cosmetic properties of the composition, the containers are attractive, have various shapes, and are provided in various sizes. The target composition may be supplied together with other skin preparations as necessary. Preferred subject compositions are characterized as being a clear liquid when applied to the skin. They are not absorbed systemically to the extent that they can be detected in the vascular system. They have been found to have no very low potential for acute irritation in standard tests and are safe for humans or other mammals. They have antibacterial action against various organisms and inhibit microbial growth in the composition. They have been found to be effective by subjective and objective tests, are expressed by the user as being moisturizing, and have a reputation. Periocular / temporal wrinkle mapping and depth measurement by laser profilometry is indicated by a reduction in the average depth of deep wrinkles in the microrelief and a significant reduction in complexity in the majority of subjects. Expresses the smoothing effect at.

  For groups of subjects that produce a p-value of less than 0.1 for about 50 days or more, the amount of wrinkles measured by laser profilometry is reduced by at least about 60-80, more typically at least about 70% of subjects, And the wrinkle depth is reduced by about 8-15%, and most commonly at least 10%.

  In clinical studies using the composition of Example 1 (although the compositions of Examples 8 and 9 were expected to work at least effectively), they were described herein without any other treatment. 9 out of 10 hairy women who used 2 ml massage of the composition once a day on the affected area, documented sufficient thinning, fading and reduced growth of face and neck hair It was.

  The following examples are given for illustration rather than limitation.

Example 1
100 g typical composition of a new skin care cosmetic preparation
0.5 g Japanese Tade extract (minimum 95% trans-resveratrol); 3,4'-trihydroxy-trans-stilbene, CAS number: [501-36-0]
0.5g Frankincense extract (Olibanum)-Bosveria serrata (60-70% triterpene), CAS number: [8050-07-5]
0.5g Extract of vegetable oil, Brassicaceae Orifera / Glycine soya (unsaponifiable fraction), CAS number: [91770-67-1]
3.0 g Vitamin E (DL-α-tocopherol acetate); 3,4-dihydro-2,5,7,8-tetramethyl-2- (4,8,12-trimethyltridecyl) -2H-1-benzopyran -6-ol acetate, 3.000 IU, CAS number: [7695-91-2]
1.2 g Vitamin A (retinol palmitate); 3,7-dimethyl-9- (2,6,6-trimethyl-1-cyclohexen-1-yl) 2,4,6,8-nonatetraen-1-ol palmi Tate, 2,000.000 IU, CAS number: [79-81-2]
2.0g Fleuridil, CAS number: [260980-89-0]
0.1 g BHT (butylhydroxytoluene), 2,6-di-tert-butyl-4-methylphenol, CAS number: [128-37-0]
5.0 g Disinfecting alcohol (isopropanol), CAS number: [67-63-0]
40.0g Refined grape seed oil, CAS number: [8024-22-4]
47.2g refined oil (cocos nucifera) capril / caprin medium chain triglyceride

Example 2
Ocular Toxicity: Effects on Eye Fibroblasts Rabbit eye fibroblasts supplemented with neutral red ex vivo were exposed to products at 15, 25, and 50% concentrations for 1 minute. Cell survival was measured by optical density. Treat the medium as a negative control. An IC50 of less than 50% is detected, indicating that the product has very low toxicity to the ocular mucosa and is comparable to commercially available products in the same field.

Example 3
Evaluation of antibacterial properties According to USPXXV, the product was tested on five strains: S. aureus, P. aeruginosa, E. coli, Candida albicans ( C. albicans), and Aspergillus niger (A. niger), based on incubation at 20 ° C. and counting on days 7, 14, 21, and 28. The antibacterial ("preservation") effect of the product is that the bacterial count (measured in concentration CFU / g) is reduced at least 2 logarithmically on day 14 and continues to decrease in the following 14 days, or at the start If it remains equal to the number (count), it is considered positive. For yeast / filamentous fungi, the counts at 14 and 28 days should be the same or lower compared to the initial count.

  Thus, the product meets USPXXV standards as effectively maintaining bacterial and fungal infertility.

Example 4
In vitro mutation determination tests are the basis for detecting cytogenetic damage that can induce the formation of micronuclei containing delayed chromosomes or fragments thereof. For this reason, three groups of SKH-1 mice (0.5, 1.5, and 4.5 ml / kg, 5 males and 5 females per group) once a day for 28 days The formulation is administered topically. Peripheral blood was collected at 36 and 48 hours after the last dose, and reticulocytes were analyzed for the presence or absence of micronuclei after staining.

  No increase in the frequency of micronucleated polychromatic erythrocytes is detected, thus judging the product as non-mutagenic.

Example 5
A 48-hour single-patch test wrinkle composition in volunteers, as a general study in 11 adult volunteers, was used for single use on the shoulder skin under a 48-hour semi-occlusive patch. It was evaluated later. Observations aimed at detecting erythema + edema are based on criteria: [M. I. I. <0.20 is non-irritating (NI); 0.20-M. I. I. <0.50 is hypoallergenic (SI); 0.50-M. I. I. <1 is moderate irritation (MI); I. I. ≧ 1 was used to calculate the acute irritation index (M.I.I.) according to a standard formula for ranking cosmetics according to irritation (I)].

  The product was classified as non-irritating (NI).

Example 6
Safety and efficacy after 28 and 56 days in volunteers On day 0, 28 and 56 of 24 volunteers,
a. Skin safety was assessed by clinical trials by dermatologists aimed at detecting signs of irritation such as erythema, edema, and hives. No significant findings were reported.
b. Laser profilometry was performed on a predetermined skin area and its wrinkles to determine maximum or average depth, complexity, amount, and isotropicity. A precision captor operating without surface contact was used to evaluate wrinkle geometric parameters and extensive skin area microrelief.

Data consists of surface complexity (or visual effect of wrinkles in%), maximum wrinkle depth (mm), amount of wrinkles (mm ³ ), and has a significance limit of p ≦ 0.05 Analyzed with a two-point t-test.

  The results are summarized in Table 4 below.

  In conclusion, the product shows a clear tendency to reduce wrinkles after 28 and 56 days. The objective findings are in line with the volunteer's subjective reports.

Example 7
Preparation of 100 g of wrinkle removing composition To 5.0 g of propan-2-ol at 60 ° C., an extract of a cadaver (90-95% resveratrol glycone), CAS number: [501-36-0] 0.5 g was added. Stir until dissolved, then add 0.5 g of olivenam extract to dissolve and set aside solution (solution A).

  2.0 g of fluridil (CAS number: [260980-89-0]) was added to 47.2 g of a medium chain triglyceride fraction of coconut oil at 40 ° C. and stirred for 20 minutes. Add 0.5 g vegetable oil extract (unsaponifiable fraction) and 0.1 g BHT, followed by 3.0 g vitamin E and 1.2 g vitamin A. The mixture is stirred until homogeneous and then solution A is added dropwise with stirring. The resulting solution functions as a storage concentrate that can be conveniently stored at up to 15 ° C. in a light-tight container sealed under a nitrogen atmosphere.

  The final formulation is prepared by adding 40 g of butter seed oil to the stock concentrate to produce 100 g of “CARE: Facial Solution” product.

  Examples of the wrinkle removal composition are as follows.

Example 8
100 g of a typical composition applicable to hirsutism ^*
1.0 g oleic oleate (octadeca-9-enoic acid octadeca-9-enyl ester), CAS number: [3687-45-4]
3.0 g Vitamin E (DL-α-tocopherol acetate); 3,4-dihydro-2,5,7,8-tetramethyl-2- (4,8,12-trimethyltridecyl) -2H-1-benzopyran -6-ol acetate, 3.000 IU, CAS number: [7695-91-2]
2.0g Fleuridil, CAS number: [260980-89-0]
5.0 g Disinfecting alcohol (isopropanol), CAS number: [67-63-0]
41.5g soybean oil, CAS number: [8001-22-7]
47.5g refined oil (cocos nucifera) capril / caprin medium chain triglycerides
^* All items except Fluidil are listed in the FDA “Inactive Ingredients Database for Approved Drug Products” (http://www.accessdata.fda.gov/scripts/ cder / iig / index.cfm).

Example 9
100 g of a representative cosmetic oil composition applicable to hirsutism ^*
2.0g Fleuridil, CAS number: [260980-89-0]
6.0 g Disinfecting alcohol (isopropanol), CAS number: [67-63-0]
42.0g Soybean oil, CAS number: [8001-22-7]
50.0 g Refined oil (Cocos Nucifera) Capril / Caprin medium chain triglyceride
^* All items except Fluidil are listed in the FDA “Approved Drug Additive Database” (http://www.accessdata.fda.gov/scripts/cder/iig/index.cfm).

Example 10
Skin composition tested for clinical hirsutism A 20-68 year old woman with facial hirsutism was admitted to the Department of Dermatology at Palatsky University Hospital in Olomouc, Czech Republic. On day 0, photographic records and blood samples are taken for serum total testosterone and sex hormone binding globulin (SHBG). Subjects were instructed to apply 2 ml of product over the affected area (upper lip, chin as needed) as a thin layer every evening. On day 90, there were no changes in hormone parameters and two dermatologists who assessed images separately concluded that hair growth, coloration, and diameter were significantly reduced in 9 subjects. . There were no local or systemic side effects.

  It is clear from the above results that the subject composition provides improved skin care. The composition functions to reduce wrinkles and damage caused by toxic substances including aging, sunlight, and smoking, and reduces unwanted facial hair growth. The composition uses ingredients that have been shown to be safe and acceptable to humans. Despite the use of a mixture of hydrophobic and hydrophilic materials, a substantially uniform mixture is obtained that can be easily applied to the skin and results in a transparent layer. The subject compositions can be used repeatedly without irritation to the skin or damage to the skin.

  All publications and patent applications cited herein are hereby incorporated by reference so that each individual publication or patent application is clearly and individually indicated and incorporated by reference.

  The foregoing invention has been described in some detail for purposes of illustration and illustration for purposes of clarity of understanding, but without departing from the spirit or scope of the appended claims. Those skilled in the art will readily understand that certain modifications and improvements are made.

Claims (17)

A skin care composition comprising cosmetically acceptable ingredients for topical treatment of wrinkles or hirsutism,
An effective amount of a physiologically acceptable 4 wherein the perfluoroacyl group is 2 to 3 carbon atoms and the propanamide group is substituted at the carbon atom at the 2-position with at least one of hydroxyl and methyl. -Nitro-3-trifluoromethylphenyl substituted perfluoroacylaminopropanamide;
An excipient comprising a large amount of at least one natural refined oil, a triglyceride oil fraction, and an alkanol of 2 to 3 carbon atoms sufficient to provide an at least substantially homogeneous mixture;
An effective amount of at least one physiologically acceptable antioxidant,
Where the composition is for the treatment of hirsutism, it optionally further comprises a humectant,
When the composition is used for treating wrinkles, the skin care composition further comprises at least one natural plant extract or a fraction thereof. The composition is for the treatment of wrinkles;
The mixture according to claim 1, comprising at least three extracts selected from the group consisting of non-saponified fractions of Japanese tade, frankincense, cruciferous orifera and / or glycine soya, fractions thereof, or synthesized equivalents. Skin care composition.   3. A skin care composition according to claim 2, wherein there are grape seeds and refined oil of Cocos nucifera.   The skin care composition according to claim 2, wherein the antioxidant is a vitamin.   The skin care composition according to claim 2, wherein the alkanol is isopropanol. The composition is for the treatment of hirsutism,
The skin care composition of claim 1 comprising refined oils of glycine soya and cocos nusifera. 0.5-5 parts by weight of 2-hydroxy-2-methyl-N- [4-nitro-3- (trifluoromethyl) phenyl] -3- (2,2,2-trifluoroacetylamino) propanamide ,
A total of 0.5 to 5 parts by weight of a Japanese extract, frankincense, and a natural extract selected from the group consisting of cruciferous orifera and / or unsaponifiable fraction of glycine soya,
50 to 95 parts by weight of grape seeds and / or cocos nucifera refined oil,
2 to 10 parts by weight of an antioxidant,
A cosmetic skin composition of cosmetically acceptable ingredients comprising 2.5 to 10 parts by weight of an alkanol of 2 to 3 carbon atoms sufficient to provide a substantially homogeneous mixture.   The cosmetic skin composition according to claim 7, wherein the antioxidants are vitamins A and E.   The cosmetic skin composition according to claim 7, wherein the alkanol is isopropanol.   The cosmetic skin composition according to claim 7, wherein there is at least one unsaponifiable fraction of Japanese tade and frankincense, and cruciferous orifera and glycine soya. 1-4 parts by weight of 2-hydroxy-2-methyl-N- [4-nitro-3- (trifluoromethyl) phenyl] -3- (2,2,2-trifluoroacetylamino) propanamide;
A total of 0.75 to 3 parts by weight of a Japanese extract, frankincense, and a natural extract selected from the group consisting of at least one unsaponifiable fraction of Brassicaceae orifera and glycine soya,
30-50 parts by weight of refined grape seed oil;
0.5-2 parts by weight of an antioxidant,
A cosmetic skin composition comprising a cosmetically acceptable ingredient comprising 3 to 7.5 parts by weight of an alkanol of 2 to 3 carbon atoms sufficient to provide a substantially homogeneous mixture. 0.5 parts by weight of 2-hydroxy-2-methyl-N- [4-nitro-3- (trifluoromethyl) phenyl] -3- (2,2,2-trifluoroacetylamino) propanamide;
0.5 parts by weight of Japanese Tade extract,
0.5 parts by weight of frankincense extract;
0.5 parts by weight of cruciferous orifera and / or glycine soya unsaponifiable fraction,
40 parts by weight of refined grape seed oil;
About 47 parts by weight of a refined oil fraction of Cocos Nucifera (medium chain triglyceride),
1.3 parts by weight of vitamin A,
3 parts by weight of vitamin E,
A cosmetic skin composition comprising 5 parts by weight of isopropanol. 0.5-5 parts by weight of 2-hydroxy-2-methyl-N- [4-nitro-3- (trifluoromethyl) phenyl] -3- (2,2,2-trifluoroacetylamino) propanamide ,
At least 80 parts by weight of refined oil of glycine soya and / or cocos nucifera,
2 to 10 parts by weight of an antioxidant,
A cosmetic skin composition comprising a cosmetically acceptable ingredient comprising 2.5 to 10 parts by weight of an alkanol of 2 to 3 carbon atoms sufficient to provide a substantially homogeneous mixture.   14. The cosmetic skin composition of claim 13, wherein the refined oil is present at 85 to 95 parts by weight, the antioxidant is tocopherol and 2 to 6 parts by weight, and a humectant is present in an effective amount.   A skin care method comprising applying the skin care composition according to claim 1 to the skin.   A skin care method comprising applying the cosmetic skin composition according to claim 12 to the skin.   A skin care method comprising applying the cosmetic skin composition according to claim 13 to the skin.